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Formation of talin-vinculin pre-complexes dictates maturation of nascent adhesions by accelerated force transmission and vinculin recruitment

Han, Sangyoon J, Dean, Kevin M, Whitewood, A.J., Bachir, Alexia, Guttierrez, Edgar, Groisman, Alexander, Horwitz, Rick, Goult, Benjamin T, Danuser, Gaudenz (2019) Formation of talin-vinculin pre-complexes dictates maturation of nascent adhesions by accelerated force transmission and vinculin recruitment. BioRxiv, . (Unpublished) (doi:10.1101/735183)

Abstract

Talin, vinculin, and paxillin are mechanosensitive proteins that are recruited early to nascent integrin-based adhesions (NAs). Using machine learning, high-resolution traction force microscopy, single-particle-tracking and fluorescence fluctuation time-series analysis, we find that, only in the NAs that eventually mature to focal adhesions, all three molecules are recruited concurrently and in synchrony with force onset. Thereafter, vinculin assembles at ~5 fold higher rates than in non-maturing NAs. We identify a domain in talin, R8, which exposes a vinculin- binding-site (VBS) without requiring tension. Stabilizing this domain via mutation lowers tension- free vinculin binding in conjunction with talin, impairs maturation of NAs, and reduces the rate of additional vinculin recruitment after force onset. Taken together, our data show that talin forms a complex with vinculin, before association with integrins, which is essential for NA maturation by talin’s effective unfolding and exposure of additional VBSs that induce fast force growth and further vinculin binding.

Item Type: Article
DOI/Identification number: 10.1101/735183
Uncontrolled keywords: Talin, vinculin, integrin, mechanobiology
Subjects: Q Science > QH Natural history > QH581.2 Cell Biology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Ben Goult
Date Deposited: 02 Sep 2019 13:26 UTC
Last Modified: 04 Sep 2019 09:09 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/76087 (The current URI for this page, for reference purposes)
Goult, Benjamin T: https://orcid.org/0000-0002-3438-2807
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